Testicular neuroendocrine tumor in a 32‐year‐old man: A case report

Key Clinical Message A 32‐year‐old male with painful scrotal swelling who underwent radical orchiectomy and was diagnosed with a testicular neuroendocrine tumor. Determining whether testicular neuroendocrine tumor is primary or metastasis from another origin is crucial. Abstract Testicular neuroendocrine tumors (TNET) are one of the rarest human neoplasms, with about 132 identified cases until 2015. Testicular neuroendocrine tumors are frequently manifest with painless scrotal swelling or mass. In this study, we present a 32‐year‐old male with a chief complaint of painful progressive swelling of the right testicle without any history of trauma. All laboratory tests were within the normal range. Ultrasound revealed two hyper‐vascular masses in the right testicle. Computed tomography was performed, and patients had no evidence of metastases. The patient underwent right radical orchiectomy, and a histopathological examination diagnosed the specimen with a well‐differentiated testicular neuroendocrine tumor. Because of the rarity of TNET, there are many controversial issues in the treatment, especially in cases with metastatic TNET. Determining whether testicular neuroendocrine tumor is primary or metastasis from another origin is crucial. Further studies are required to achieve optimum treatment for TNET.


| INTRODUCTION
Testicular cancer is one of the infrequent malignancies with incidence of about 1% among male individuals.Around 95% of testicular cancers arise from germ cell tumors, the most frequent type. 1 Further, the testicle is an infrequent location for developing neuroendocrine tumors, as less than 1% of testicular tumors are identified to have a neuroendocrine nature.In contrast, most neuroendocrine tumors are found in the gastrointestinal tract.So, testicular neuroendocrine tumors (TNET) are one of the rarest neoplasms, with about 132 identified cases until 2015. 2 Similar to other testicular neoplasms, TNETs are frequently manifested with painless scrotal swelling or mass, whether testicular neuroendocrine tumor is primary or metastasis from another origin is crucial.

Abstract
Testicular neuroendocrine tumors (TNET) are one of the rarest human neoplasms, with about 132 identified cases until 2015.Testicular neuroendocrine tumors are frequently manifest with painless scrotal swelling or mass.In this study, we present a 32-year-old male with a chief complaint of painful progressive swelling of the right testicle without any history of trauma.All laboratory tests were within the normal range.Ultrasound revealed two hyper-vascular masses in the right testicle.Computed tomography was performed, and patients had no evidence of metastases.The patient underwent right radical orchiectomy, and a histopathological examination diagnosed the specimen with a well-differentiated testicular neuroendocrine tumor.Because of the rarity of TNET, there are many controversial issues in the treatment, especially in cases with metastatic TNET.
Determining whether testicular neuroendocrine tumor is primary or metastasis from another origin is crucial.Further studies are required to achieve optimum treatment for TNET.

K E Y W O R D S
carcinoid tumor, neuroendocrine tumors, testicular cancer, testicular neuroendocrine tumor while about 10% of reported cases had carcinoid syndrome, which is characterized by flushing, chronic diarrhea, abdominal pain, bronchospasm, and sweats. 2,3The median age at the time of diagnosis is 38 years, serum biomarkers including βgonadotrophin chorionic humaine, αfeto protein, and lactate dehydrogenase are usually not elevated, and about 6% of TNETs are metastatic at the time of diagnosis. 2In this study, we aim to present a case of TNET and highlight the diagnosis and management process.

| CASE HISTORY
A 32-year-old male presented to the urology Department of the Firoozgar Hospital (Tehran, Iran) with a two-month history of painful progressive swelling of the right testicle.The patient denied any history of trauma or previous scrotal surgeries.His past medical and familial history was not notable.

| Physical examination and laboratory tests
Physical examination revealed an enlarged right testicle and tenderness on palpation.The epididymal demarcation was distinct, and no inguinal lymphadenopathy was identified.Also, laboratory tests, including complete blood count, liver function tests, renal function tests, and tumor markers including αfetoprotein (2.06 ng/mL), beta-human chorionic gonadotropin (0.1 IU/L), and lactate dehydrogenase (376 U/L) were within normal limits.

| Differential diagnoses, investigations, and treatment
As shown in Figure 1, scrotal 10 MHz ultrasound revealed a solid hyperechoic mass within the inferior part of the right testicle (diameter: 36 × 44 × 32 mm) and another solid cystic mass (diameter: 49 × 45 × 63 mm) at the upper portion of the right testicle.Also, in the Doppler examination, both masses were hyper-vascular.Also, a moderate hydrocele was identified in the right hemi-scotoma.A chest, abdomen, and pelvic computed tomography (CT) scan and bone scintigraphy were performed after the operation to assess the possible metastases, and no evidence of metastasis was identified.Also, the patient underwent an endoscopy and colonoscopy to explore the gastrointestinal tumor; however, it was negative.
Based on the ultrasound results, the patient underwent right radical orchiectomy, and the specimens, including spermatic cord (3.5 × 3 cm), tumors, epididymis (15 × 1 cm), and right testicle (12.5 × 7 × 7 cm), were sent for histopathological examinations.A well-defined homogeneous cream-yellow rubbery mass (diameter: 6 × 5.5 × 5 cm) with a cystic attached area to the lateral portion (35 mm in greatest diameter) was identified.Tunica vaginalis, epididymis, spermatic cord, and surgical margin were tumors-free.In the testicular tissue, the islands of cells for mainly small acini and cords or mainly sheets separated by fibrous stroma were identified.The cells had granular eosinophilic cytoplasm round nuclei with granular chromatin, and no significant mitotic activity or necrosis was identified.
Immunohistochemistry staining showed negative reactivity for SALL4, CD117, CDX2 and TTF1.In contrast, positive reactivity for Plap, CD56, INSM1, and Synaptophysin were identified.KI67 was estimated to be up to 2%.Also, Chromogranin showed weak positive reactivity.As shown in Figure 2, the histopathological examination revealed a well-differentiated neuroendocrine tumor (mono-dermal teratoma).

| Outcome and follow-up
During 1 year of follow-up, no distinct metastasis was identified, and the patient had no post-surgical complications.TNET was first introduced by Simon et al. in 1954. 4However, TNETs are known as carcinoid tumors.TNET is extremely rare, with a mean prevalence of less than 1% among testicular tumors.According to the latest World Health Organization classification for testicular tumors, TNET is a subtype of germ cell tumors unrelated to germ cell neoplasia. 5he mean age at the diagnosis is 39 years, ranging from 10 to 83 years.The most common symptom is the painless scrotal mass; however, about 17% of patients present with scrotal pain.About 10% of patients are diagnosed with carcinoid syndrome; however, it is uncommon.Serum tumor markers such as βgonadotrophin chorionic Hormone, αfeto protein, and lactate dehydrogenase are within the normal range as in our patient.Among TNETs, primary TNET is the most common one; however, about 7% of TNETs are metastatic tumors of another origin.Also, about 16% of TNETs are associated with testicular teratoma. 2,6ame as other testicular tumors, ultrasound is an available and accurate modality for pre-operative evaluation.However, abdominopelvic magnetic resonance imaging (MRI) and CT-scan can be used to find other sites metastasis.As a testicular mass, the standard treatment for the TNETs is orchiectomy.In cases of lymph node metastasis, patients should undergo retroperitoneal lymph node dissection.Patients with metastatic TNETs should undergo combination therapy with streptozocin, 5-fluorouracil, and cyclophosphamide (or doxorubicin) as the standard chemotherapy protocol.9][10][11] In conclusion, because of the rarity of the TNET, there are many controversial issues in the treatment, especially in cases with metastatic TNET.Determining whether TNET is primary or metastasis from another origin is crucial.Further studies are required to achieve optimum treatment for TNETs.

F I G U R E 1
Testicular ultrasound: (A) solid heterogenic mass within the inferior part of the right testicle (diameter: 36 × 44 × 32 mm), (B) moderate hydrocele in the right hemi-scotoma, (C) another solid heterogenic mass (diameter: 63 × 49 × 45 mm) at the upper portion of the right testicle.